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Gene Therapy Clinical Study in Adult PKU (pheNIX)

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ClinicalTrials.gov Identifier: NCT03952156
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : October 11, 2021
Sponsor:
Information provided by (Responsible Party):
Homology Medicines, Inc

Study Description
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Brief Summary:
This is a Phase 1/2, open-label, randomized, concurrently-controlled, dose escalation study to evaluate the safety and efficacy of HMI-102 in adult PKU subjects with PAH deficiency. Participants will receive a single administration of HMI-102 and will be followed for safety and efficacy for 1 year.

Condition or disease Intervention/treatment Phase
Phenylketonurias PAH Deficiency Genetic: HMI-102 Phase 1 Phase 2

Detailed Description:

Part 1 of this study will evaluate the safety and efficacy of HMI-102 gene therapy in adult subjects with PKU due to PAH deficiency. Subjects will receive a single dose of HMI-102 administered intravenously. Up to 3 dose levels of HMI-102 may be investigated in this study. At a given dose level, a minimum of 2 subjects will be enrolled and dosed. Dosing of the first two subjects will be staggered. Following evaluation of data from the first 2 subjects in a cohort, a decision can be made to either escalate to the next dose level or expand the cohort at the selected dose level. Additional doses may be added by HMI to investigate intermediate or higher doses.

In Part 2 dose expansion, evaluation of up to 2 dose levels is planned. Subjects will be randomized to receive HMI-102 or a concurrent delayed treatment control arm. Subjects in the delayed treatment control will be eligible to receive HMI-102 after 28 weeks.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Open-Label, Randomized, Concurrently-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of HMI-102 in Adult PKU Subjects With PAH Deficiency
Actual Study Start Date : June 10, 2019
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : September 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Phenylketonuria

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1
Dose Level 1 of HMI-102 delivered intravenously one time
 Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 2
Dose Level 2 of HMI-102 delivered intravenously one time
 Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Cohort 3
Dose Level 3 of HMI-102 delivered intravenously one time
 Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Delayed Treatment Control
Delayed Treatment Control Arm
 Genetic: HMI-102

Control subjects will generally have the same assessments as treated subjects.

Control subjects will undergo pre-baseline procedures to confirm that they are eligible to receive treatment with HMI-102. Once eligible control subjects are dosed with HMI-102, they will initiate the same post-dose procedures as subjects who received HMI-102.
Experimental: Expansion Phase First Dose level
Expansion Phase First Dose Level of HMI-102 delivered intravenously one time
 Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene
Experimental: Expansion Phase Second Dose level
Expansion Phase Second Dose Level of HMI-102 delivered intravenously one time
 Genetic: HMI-102
HMI-102 is an AAVHSC15 vector containing a functional copy of the human PAH gene


Outcome Measures
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Primary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
    Subjects with at least one TEAE or serious TEAE

  2. Change from baseline in clinical laboratory values (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
    Change in serum chemistry values including liver function tests, hematology, and urinalysis

  3. Change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations (Dose Escalation Phase) [ Time Frame: Baseline to Week 52 ]
    Subjects change from baseline in 12-lead electrocardiograms (ECGs), vital signs, physical examinations

  4. Incidence of sustained plasma Phe concentration of ≤360 μmol/L at 28 weeks post dose (Dose Escalation Phase) [ Time Frame: Week 28 ]
    Subjects achieving a sustained plasma Phe concentration ≤360 μmol/L at 28 weeks post dose

  5. Change from baseline in Plasma Phe Concentration (Dose Escalation Phase) [ Time Frame: Weeks 24-28 ]
    Change from baseline in plasma Phe concentration during Weeks 24-28

  6. Change from baseline in mean Plasma Phe Concentration (Dose Expansion Phase) [ Time Frame: Weeks 24-28 ]
    Change from baseline in mean plasma Phe concentration during Weeks 24-28


Secondary Outcome Measures :
  1. Incidence of plasma Phe concentration thresholds up to Week 28 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 28 ]
    Subjects achieving plasma Phe concentration thresholds up to Week 28 post administration of HMI-102

  2. Incidence of plasma Phe concentration thresholds up to Week 52 post administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]
    Subjects achieving plasma Phe concentration thresholds up to Week 52 post administration of HMI-102

  3. Change from baseline in total protein intake at Week 52 post-administration of HMI-102 (Dose Expansion Phase) [ Time Frame: Week 52 ]
    Subject Achieving a change from baseline in total protein intake at Week 52 post-administration of HMI-102

  4. Incidence and severity of treatment-emergent adverse events (TEAEs) (Dose Expansion Phase) [ Time Frame: Baseline to Week 52 ]
    Subjects with at least one TEAE or serious TEAE


Other Outcome Measures:
  1. Phenylketonuria Quality of Life Questionnaire (PKU-QOL) [ Time Frame: Baseline to Week 52 ]
    Change in PKU-QOL


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Adults 18-55 years of age at the time of informed consent
  • Diagnosis of phenylketonuria (PKU) due to PAH deficiency
  • Two plasma Phe values with a concentration of ≥ 600 μmol/L drawn at least 72 hours apart during the screening period and at least one historical value ≥ 600 μmol/L in the preceding 24 months.
  • Subject has the ability and willingness to maintain their baseline diet, whether Phe-restricted or unrestricted for the duration of the trial, unless otherwise directed

Key Exclusion Criteria:

  • Subjects with PKU that is not due to PAH deficiency
  • Presence of anti-AAVHSC15 neutralizing antibodies
  • ALT > ULN and AST > ULN
  • Alkaline phosphatase > ULN.
  • Total bilirubin > ULN, direct bilirubin > ULN
  • Serum creatinine >1.5x ULN
  • International normalized ratio (INR) > 1.2
  • Hematology values outside of the normal range (hemoglobin <11.0 g/dL for males or <10.0 g/dL for females; white blood cells (WBC) <3,000/μL; absolute neutrophils <1500/μL; platelets <100,000/μL)
  • Hemoglobin A1c >6.5% or fasting glucose >126 mg/dL
  • Any clinically significant abnormal laboratory result at screening, in the opinion of the Investigator
  • Contraindication to corticosteroid use or conditions that could worsen in the presence of corticosteroids, as assessed and determined by the investigator
  • Previously received gene therapy for the treatment of any condition.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03952156


Contacts
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Contact: Julie Jordan, M.D. 781-819-0967 clinicaltrials@homologymedicines.com

Locations
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United States, California
Kaiser Permanente Los Angeles Medical Center Recruiting
Los Angeles, California, United States, 90027
Contact: Olivia Bravo    323-783-1542    olivia.bravo@kp.org   
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Harriet Chang    714-509-8300    Huiyi.Harriet.Chang@choc.org   
United States, Florida
University of South Florida Recruiting
Tampa, Florida, United States, 33606
Contact: Farideh Oberheu    813-250-2292    faljalla@usf.edu   
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Eleanor Botha    404-778-8517    egeller@emory.edu   
United States, Illinois
Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Carolyn Ries    312-227-6004    CRies@luriechildrens.org   
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eorna Maguire    617-919-1399    Eorna.Maguire@childrens.harvard.edu   
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: Catherine Miller    212-659-1456    Catherine.miller@mssm.edu   
United States, North Carolina
The University of North Carolina At Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Chen Zhu    919-966-1447    czhu@email.unc.edu   
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Candice Roush    614-722-2512    Kandice.roush@nationwidechildrens.org   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Erika Rodriquez-Guzman    225-241-8993    RODRIGUEE4@EMAIL.CHOP.EDU   
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jennifer Baker    412-692-6378    Jennifer.Baker@chp.edu   
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75235
Contact: Kellyn Pollard    214-645-7415    Kellyn.Pollard@UTSouthwestern.edu   
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84108
Contact: Carrie Bailey    801-587-3605    Carrie.Bailey@hsc.utah.edu   
Sponsors and Collaborators
Homology Medicines, Inc
Investigators
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Principal Investigator: Olaf A Bodamer, M.D. Boston Children's Hospital
More Information
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Responsible Party: Homology Medicines, Inc
ClinicalTrials.gov Identifier: NCT03952156    
Other Study ID Numbers: HMI-102-101
First Posted: May 16, 2019    Key Record Dates
Last Update Posted: October 11, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Homology Medicines, Inc:
PKU
Phenylketonuria
PAH Deficiency
Hyperphenylalaninemia
 Phenylalanine
Adeno Associated Virus
AAVHSC15
Additional relevant MeSH terms:
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Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases